Acute and recurrent diseases caused by herpesviruses are among the most common and often most serious infections in man. Herpes simplex virus and cytomegalovirus are two of the most important of these agents. We propose to further define the pathogenesis of these viruses, particularly the mechanisms associated with latent and recurrent infections, by employing herpes simplex virus and murine cytomegalovirus in the mouse and in cell culture systems. In the herpes simplex studies, temperature sensitive mutants of the virus with defined phenotypes will be employed in mice to determine biochemical events necessary for establishment of latent infections. In addition, extensive attempts will be made to establish latent infections in cultures of differentiated neuroblastoma cells with both wild-type and temperature sensitive viral mutants. We have established latent cytomegalovirus infections in mice, and have succeeded in reactivating these infections with antilymphocyte serum and cortisone. Now, we propose to extend these findings by 1) defining the cell-types involved in harboring latent virus, 2) determining the conditions and mechanisms by which reactivation occurs, and 3) investigating the efficacy of various therapeutic regimens.